Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical-stage gene editing company using its proprietary ARCUS® platform for advanced in vivo gene editing therapies, announced a poster presentation at the European Society of Gene & Cell Therapy (ESGCT) 31st Annual Congress, taking place from October 22-25, 2024, in Rome, Italy. The poster showcased preclinical data demonstrating ARCUS’s capability for high-efficiency gene insertion, gene replacement, and base correction through homology-directed repair (HDR).
“Gene editing enzymes that facilitate efficient homology-directed repair (HDR) are quite rare. However, we demonstrate that ARCUS can effectively utilize HDR to achieve various gene editing outcomes, including specific base changes, insertions, and the replacement of large DNA segments within the genome,” said Jeff Smith, PhD, Co-Founder and Chief Research Officer of Precision BioSciences. “These results further validate the ARCUS platform as an ideal approach for treating diseases that require gene insertion or repair, in contrast to other modalities that primarily focus on knocking out functions. In addition to the preclinical data presented today, we are eager to see clinical validation of HDR-based ARCUS gene insertion through our partner iECURE, which is advancing the ECUR-506 clinical program utilizing an ARCUS nuclease for treating OTC deficiency.”
Title: High-Efficiency Homology-Directed Insertion into the Genome Using ARCUS Nucleases
Poster Number: #PO678
Presenter: Adam Mischler, PhD, Senior Scientist, Precision BioSciences Gene Discovery
Date and Time: Thursday, October 24, 2024, 6:00-7:30 PM CEST
The preclinical data presented today showed that targeted gene insertion using ARCUS was achieved in over 85% of T cells and 39% of non-dividing primary human hepatocytes. These high rates were primarily attributed to HDR, as demonstrated by the dependency on homology arms in the repair template and the unique ARCUS 3’ 4-base pair overhang cut, which stimulates HDR.
ARCUS demonstrated the capability to support various DNA editing approaches using a template for specific edits. Unlike base editors, which are limited to two potential base changes, ARCUS achieved all twelve possible base changes and specific base removals and insertions. Additionally, ARCUS outperformed prime editors by facilitating whole gene insertions and the replacement of large gene segments to restore function. The distinctive enzymology of ARCUS nucleases drives high HDR rates, potentially enabling a wide range of precise gene editing functions for therapeutic benefits.
About Precision BioSciences, Inc.
Precision BioSciences is an advanced gene editing company focused on improving lives through its proprietary ARCUS genome editing platform. This platform is distinct in its cutting mechanism, smaller size, and simpler structure. ARCUS nucleases are designed to achieve intended therapeutic outcomes more effectively. The company’s pipeline includes in vivo gene editing candidates aimed at providing lasting cures for various genetic and infectious diseases where adequate treatments are currently lacking.
The ARCUS platform is being employed to develop in vivo gene editing therapies for complex edits, including gene insertion, elimination (such as removing viral DNA or mutant mitochondrial DNA), and excision (removing large portions of defective genes using two ARCUS nucleases delivered in a single AAV).
